The long-range objectives of the Colorado Learning Disabilities Research Center (CLDRC) are the identification, characterization, validation and amelioration of reading disabilities (both word-level and comprehension), writing disabilities (both writing mechanics and composition), and ADHD, the most prevalent and often co-morbid disorders of childhood. To accomplish these objectives, the CLDRC employs a unique approach that assesses the extent to which genetic and environmental influences underlie these disorders, and that uses covariation in etiology to understand whether deficits in component skills of reading and writing are manifestations of a single syndrome or represent separate subtypes. Test batteries that include psychometric measures of cognitive and academic abilities and processing speed (Project I), word reading, writing, and phonological processes (Project II), ADHD and executive functions (Project III), and reading and listening comprehension (Project V) will be administered to a sample of identical and fraternal twins and their siblings in which at least one member of each twin pair has a reading or writing disability, to an independent sample of twins and their siblings in which at least one member of each twin pair has ADHD, and to a comparison group of twins and their siblings with no school history of reading or writing disabilities or ADHD. Resulting data will be used to assess the etiologies of reading and writing deficits and ADHD, and their comorbidity, as well as their covariation with measures of phonological awareness, phonological decoding, orthographic coding, vocabulary, listening comprehension, processing speed, and executive functions. Project VI will address these questions longitudinally in the CLDRC sample and in a parallel unselected sample of twins. To identify causal mutations in genes and regulatory regions, deep sequencing will be performed from DNA samples extracted from saliva from families of all twin pairs and siblings (Project IV). Administrative and Service core units will be responsible for coordinating the activities of the si research projects, ascertaining and scheduling subjects, obtaining questionnaire data and saliva samples, disseminating data, supervising student training, and administering the Center budget. PUBLIC HEALTH RELEVANCE: Reading and writing disabilities and ADHD are important public health problems. The proposed research will advance our understanding of their differential diagnosis, comorbidity, and etiology, with implications for early identification and intervention.